Patent EA-000695-B1 (EA)
Title: Optically active phenyl pyrimidine derivatives, production thereof and use thereof as analgesic agent
Inventor: NOBBS MALCOLM STUART
IPC: A61K31/505
Filed: 1996-09-03
Abstract: 1. A pyrimidine of formula (I)   or an acid addition salt thereof. 2. A salt according to claim 1, which is a pharmaceutically acceptable acid addition salt. 3. A salt according to claim 1 which is the sulphate, phosphate or isethionate salt. 4. A salt according to claim 1 which is the hydrochloride or methanesulphonate salt. 5. A process for the preparation of a pyrimidine of formula (I) as defined in claim 1 or an acid addition salt thereof, which process comprises (i) racemic 2,4-diarmino-5-(2,3-dichlorophenyl)-6-fluoromethyl pyrimidine with a suitable chiral acid and recrystallising the resulting salt so as to obtain a salt which consists substantially only of the salt with R(-)-2,4-diamino-5-(2,3-dichlorophenyl)-6-fluoromethyl pyrimidine; and (ii) if desired, converting the recrystallised salt to the free base or another acid addition salt as appropriate. 6. A process for the preparation of a pyrimidine of formula (I) as defined in claim 1 or an acid addition salt thereof, which process comprises: (a) racemic 2,4-diamino-5-(2,3-dichlorophenyl)-6-hydroxymethyl pyrimidine with a suitable chiral acid and recrystallising the resulting salt so as to obtain a salt which consists substantially only of the salt with (-)-2,4-diamino-5-(2.3-dichlorophenyl)-6-hydroxy methyl pyrimidine; (b) if desired, converting the recrystallised salt to the free base or another salt; (c) fluorinating the recrystallised salt from step (a) or the free base or said other salt from step (b) under conditions at which racemisation of the (-)-2,4-diamino-5-(2,3-dichlorophenyl)-6-hydroxymethyl pyrimidine or the resulting (-)-2,4-diamino-5-(2,3-dichlorophenyl)-6-fluoromethyl pyrimidine does not occur; and (d) if desired, converting the resulting fluorinated compound into the free base or into an acid addition salt thereof as appropriate. 7. A pharmaceutical formulation comprising, as active ingredient, a pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier or diluent. 8. A pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof, for use in therapy. 9. A pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof for use in the manufacture of an analgesic. 10. A pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof for use in the manufacture of an anticonvulsant medicament for the treatment of irritable bowel syndrome or bipolar disorder. 11. A pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof for use in the manufacture of medicament for the treatment of irritable bowel syndrome or bipolar disorder. 12. A pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof for use in the manufacture of medicament for the treatment of bipolar disorder. 13. A pyrimidine of formula (I) as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof, for use in the manufacture of a medicament for the treatment of functional bowel disorders, bipolar disorder or neurodegenerative disorders, or a medicament for preventing or reducing dependence on, or preventing or reducing tolerance to, a dependence-inducing agent. 14. A pyrimidine of formula (III)